amfAR Consortium Helps Lead Efforts for HIV/AIDS Cure

Second year of grants builds on momentum

NEW YORK, June 16, 2011—Building on momentum from its first round of cure-focused grants issued last year, amfAR, The Foundation for AIDS Research, on Thursday announced a second round of grants that will enable some teams to continue their groundbreaking research while adding two additional, promising projects aimed at unlocking more information about how to potentially eradicate HIV infection.

The second round of funding for the amfAR Research Consortium on HIV Eradication (ARCHE) comes one year after the launch of the program, and after several of the researchers have already made important scientific progress via connections with other ARCHE members.

“After just one year of bringing these researchers together and encouraging them to share their data and insights, we’ve seen great strides in our collective understanding of how HIV could potentially be eradicated,” said amfAR CEO Kevin Robert Frost. “There is more hope than ever that we’re on the right path to a cure for HIV/AIDS, and amfAR is proud to be at the forefront of accelerating those research efforts.”

Building on research connections made through ARCHE last year, Dr. Adriana Andrade of Johns Hopkins University, new to the ARCHE consortium, will test the ability of disulfiram—a drug approved by the US Food and Drug Administration to treat alcoholism—to drive the virus out of infected cells in a small clinical study. Dr. Bob Siliciano, during his first year of ARCHE funding, identified and characterized the drug as an agent that might flush virus out of latently HIV-infected cells. Collaborating with Dr. Janice Clements, also of Johns Hopkins, he will continue to investigate other FDA-approved drugs for their effect on latent HIV during his second year of funding.

Dr. Mike McCune of the University of California, San Francisco, collaborating with Dr. Steven Deeks, will continue to examine the role of ongoing activation of the immune system—long suspected of playing a role in HIV disease—in the ability of HIV to persist during the lifetime of an infected patient. They will also test an FDA-approved drug that could play an integral role in a potential new therapeutic strategy that could bring us closer to a functional cure.

Collaborating with the ARCHE investigators at UCSF, including Drs. Steven Deeks and Frederick Hecht, second-time ARCHE grantee Dr. Sarah Palmer of the Swedish Institute for Infectious Disease Control and Karolinska Institutet will continue to investigate which cellular reservoirs are most responsible for the persistence of HIV. These findings will inform efforts by the Siliciano/Clements and McCune/Deeks ARCHE groups by identifying the important targets of their efforts to purge reservoirs of virus or to modulate immune activation to effect a cure.

“The progress of our ARCHE researchers is a testament to the importance of collaboration in HIV research and getting researchers to share ideas and data,” said Dr. Rowena Johnston, amfAR’s vice president and director of research. “We’re tremendously excited by this consortium. And we’re confident that this collaborative approach will continue to create synergies that produce results that exceed what can be generated in individual laboratories.”

Finally, as researchers in ARCHE and elsewhere draw closer to discovering methods to reduce the size of the viral reservoir, sensitive methods for measuring changes in its size will be needed. The other new ARCHE grantee, Dr. Una O’Doherty of the University of Pennsylvania, will compare methods for measuring HIV reservoir size to determine which are the most accurate and practical. The persistent reservoir of virus constitutes a tiny fraction of all the virus present, but understanding how to measure changing levels of virus in the reservoir is difficult—and crucial to determining the next steps in HIV eradication.

amfAR’s public commitment to a cure for HIV/AIDS helped catalyze the surge of interest in cure research during the past several years. In January the International AIDS Society announced plans to create its own cure consortium, co-chaired by ARCHE grantee Dr. Steven Deeks, and the National Institutes of Health will announce the creation of its cure consortium later this year. More than ever, scientists believe that investing in a cure for HIV/AIDS will increasingly pay off.

ARCHE-funded research teams and their projects are as follows:

Adriana Andrade, M.D., MPH
Johns Hopkins University, Baltimore, MD
$112,000
Disulfiram to accelerate decay in HIV reservoirs in ART treated patients:Disulfiram, a drug approved by the US Food and Drug Administration to treat alcoholism, was recently identified in a test tube as a drug that might flush virus out of latently HIV-infected cells. As such, it may play a role in helping identify strategies to one day cure HIV. Dr. Andrade plans to test the ability of disulfiram to mobilize the virus out of infected cells in a small clinical study taking place at two sites, in Baltimore and San Francisco. The outcome of this trial will determine whether test tube studies accurately predict patient outcome and ultimately the role of such a strategy in potentially curing HIV infection.

University of California San Francisco, San Francisco, CA
Mike McCune, M.D., Ph.D. – principal investigator
Steven Deeks, M.D. – collaborating investigator
$270,000
Inflammation and HIV persistence:Drs. McCune and Deeks will continue to investigate the contribution of ongoing immune activation to the ability of HIV to persist. They hypothesize that a self-perpetuating, looping chain of events is established soon after HIV infection first occurs. The immune system is activated as it attempts to combat the infection, but this immune activation in turn fuels the ability of the virus to replicate and persist, resulting in a situation in which immune activation and viral replication feed one another. One particularly important site for immune activation is the gut, where immune cells retain high levels if inflammation even when the virus is well controlled by antiretroviral therapy. Drs. McCune and Deeks will test whether a drug already approved by the FDA to treat ulcerative colitis, mesalamine, will affect levels of inflammation in the gut and in turn reduce the ability of HIV to persist during antiretroviral therapy. If their hypothesis is correct, the results will point to a potential new therapeutic strategy that could both decrease levels of immune activation— itself associated with some of the disease conditions commonly seen in HIV infection— and lower the amount of virus that persists, bringing us closer to a functional cure.

Una O’Doherty, M.D., Ph.D.
University of Pennsylvania, Philadelphia, PA
$120,000
Comparing methods to measure reservoir size:The greatest barrier to curing HIV is the existence in all patients of a persistent reservoir of virus that constitutes a tiny fraction of all the virus present. Because this reservoir is present in only approximately one in a million infected cells, measuring the levels of the reservoir, and especially changes in the size of the reservoir, is technically very challenging, yet crucial for evaluating the effectiveness of potential methods to cure HIV. Dr. O’Doherty plans to compare different methods for measuring reservoir size to determine which are the most accurate and practical.

Swedish Institute for Infectious Disease Control and Karolinska Institutet, Solna, Sweden
Sarah Palmer, PhD. – principal investigator
Frederick Hecht, MD. – collaborating investigator
$270,000
Characterizing and targeting persistent HIV viremia:Dr. Palmer will continue to work with Dr. Hecht to analyze HIV found in blood and tissue samples of patients who initiated antiretroviral therapy either during acute HIV infection or later. Genetic sequences of plasma viruses will be compared to the sequences of viruses isolated from peripheral blood cells, cells in the gastrointestinal tract, and the bone marrow. Building on findings during their first year of funding, they will analyze additional types of tissue, specifically from lymph nodes, and will more closely characterize which subsets of T cells harbor persistent reservoirs of virus and under which conditions. Their goal is to identify which cells produce the virus that is routinely measured in plasma, virus that persists despite very effective antiretroviral therapy. This study will help define where the persistent plasma virus is being produced. These studies together will provide an indication of which reservoirs are most responsible for the persistence of the virus, the extent to which antiretroviral therapy can and cannot disrupt those reservoirs, and therefore what remains to be done in targeting reservoirs to cure HIV infection.

Johns Hopkins University, Baltimore, MD
Robert Siliciano, M.D., Ph.D. – principal investigator
Janice Clements, Ph.D. – collaborating investigator
$270,000
Using approved drugs to target latent HIV:Because HIV can persist indefinitely in reservoirs in an infected individual, eradicating HIV will require flushing virus out of those reservoirs and then targeting it with antiretroviral therapy. Developing new therapeutic agents, such as ones that might flush out latent HIV, can be a timely and costly enterprise, so Drs. Siliciano and Clements are hoping to identify drugs that are already FDA-approved and available for the treatment of other conditions that could be used in the context of HIV infection. During the first year of their funding they identified a promising agent, disulfiram, that they plan to test in a non-human primate model to determine whether such agents might reduce the amount of virus that is growing or the number of cells that are harboring latent HIV. This model will also allow them to test whether and how latently infected cells throughout the body are affected by such drugs. They will also compare different test tube models for identifying promising drug compounds to characterize those methodologies that best predict which drugs will be most effective in patients. If successful, these studies could point the way to strategies that could shorten the development time of interventions to cure HIV infection by ten or more years.

About amfARamfAR, The Foundation for AIDS Research, is one of the world’s leading nonprofit organizations dedicated to the support of AIDS research, HIV prevention, treatment education, and the advocacy of sound AIDS-related public policy. Since 1985, amfAR has invested nearly $325 million in its programs and has awarded grants to more than 2,000 research teams worldwide.